Steroid compounds and process



United States STEROID COMPOUNDS AND PRGCESS Robert H. Levin and Barney i. l /iagerlein, Kalamazoo, Mich, assignors to The Upjohn Company, Kalamazoo, Mich., a corporation of Michigan No Drawing. Application November 29, 1951 Serial No. 259,0li8

Claims. (Cl. 269-23955) which is of the beta or normal stereochemical configuration. It is another object of the present invention to provide a process for the preparation of 3,1 lB-dihydroxypregnane-ZO-one-ZO-ketals and also hydrolysis of these 3,1lfl-dihydroxypregnane--one'20-ketalsto produce 3,1lfi-dihydroxypregnane-20-ones.- An additional object of the present invention is to provide the novel 3,1 lfi-dihyhydroxypregnane-ZO-one-ZO-ketals. Other objects of the present invention will be apparent to those skilled in the art to which this invention pertains.

The novel 3,1lfi-dihydroxypregnane-ZO-one-ZO-ketal compounds and the known 3,1lfl-dihydroxypregnane-ZO- ones produced by the method of the present invention are useful in the synthesis of certain physiologically-active steroids containing an llp-hydroxy group, such as is present in the cortical hormones l7a-hydroxycorticosterone and corticosterone, as shown by Von Euw, Lardon, and Reichstein, Helv. Chim. Acta, 27, 1287 (1944). Likewise, the novel process of the present invention has utility in the synthesis of cortical hormones containing the llp-hydroxy group since it relates to the hydrogenar tion of the ll-keto substituent of 3-hydroxypregnane- 11,20-dione-20-ketal. The importance or" this novel process and the novel llfi-hydroxy ketal compounds produced is emphasized by the acute shortage of adrenal cortical hormones and the absence of any present suggestion for alleviation of the said shortage except through organic synthesis.

According to the novelhydrolysis method of the present invention, a 3,1lfl-dihydroxypregnane-20-one-20- alkane diol ketal, wherein the 20-ketal group contains from two to eight carbon atoms, inclusive, is hydrolyzed by a process which includes mixing an acid hydrolyzing agent and the llp-hydroxy steroid ketal in an aqueous organic solvent mixture, the organic solvent of which is non-reactive under the conditions of reaction, at a ternperature between about zero degrees centigrade and the boiling point of the reaction mixture, and separating the 3,1l,8-dihydroxypregnane-20-one from the reaction product.

The novel compounds of the present invention are the atom G i 2,824,871 Patented Feb. 25, 1958 r ce having the wherein R is selected from the group consisting or n, drogen and lowcr-alkyl groups, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, l-methylpropyl, amyl, hexyl and the like, and n is an integer from one to two, inclusive. Of these compounds, the lower alkylene glycol ketals, formed from the 1,2-alkane-diols, are preferred. The configuration of the hydroxy group at the 3-position includes both alpha and beta forms in the above formula and throughout the specification and appended claims, unless otherwise specified.

The novel llfi-hydroxy ketal compounds of the present invention are prepared by a reduction process which includes mixing a reducing agent such as, for example, lithium aluminum hydride, in excess of the amount theoretically required, and a starting B-hydroxypregnane- 11,20-dione-20-alkane diol ketal, in an organic solvent which is non-reactive under the conditions of reaction, at a temperature between about zero and about de-. grees centigrade, hydrolyzing the reaction product and separating the 3,11,8-dihydroxypregnane-ZG-one-ZO-ketal thus-produced.

The starting compounds employed in the method of the present invention are the 3-hydroxypregnane-1LZO- dione-ZO-ketals having the following structural formula:

CH3 O-(Clih) i a 0% CH:

wherein R is selected from the group consisting of hydrogen and lower-alkyl sucn as, for example, methyl, ethyl, propyl, iso propyl, butyl, 1-methylpropyl,amyl, hexyl and the like, 11 is an integer from one to two, inclusive, and the configuration of the 3-hydroxy group is alpha or beta.

The starting ketals in turn are prepared by a process which includes mixing, in a proportion of at least about one mole to one, a ketal forming reagent selected from the group consisting of alkane-LZ-diols and alkane-1,3-diols such as, for example, ethylene glycol, propane-1,2-diol, propane-1,3-diol, hexane-1,3-diol, octane-1,2-diol and the like, and a 3-hydroxypregnane-l1,20-dione in the presence of an organic sulfonic acid or a mineral acid, at a temperature below about 208 degrees Centigrade, to cause conversion of the ZO-keto group to a ZO-ketal group. The 3a-hydroxypregnane-l1,20-dione is a compound known in the prior art. The procedure utilized in the formation of the starting materials is illustrated morefully in the preparations.

in carrying out the novel reduction process of the i I 'cohol and the like.

.ter and solvent is satisfactory; r V The reaction may be conducted at a temperature 'between about zero degrees centigrade and the boiling point 'ing point being preferred.

Ha A

present invention to produce a novel 3,11,8-dihydroxypregnane-20-one-20-ketal, a starting 3-hydroxypregnane-' 11,20-dione-20-ketal is admixed, using either order of addition, with at leastthe theoretical amount of reducing agent such as, 'for example, lithium alu minuni hydride, sodium'bo'rohydride, or lithium borohydride, in an organic solvent which is non-reactive'under the reaction conditions,.at a t err'ipe'rature below about 100 degrees centigrade, preferably, between about zero and about 80 degrees centigrade. Ordinarily, 'it is preferred to use an excess of reducing agent, preferably between about five and about twenty moles of reducing agent per mole of the starting- 3-hydroxypregnane-1 1,20-dione-20-ketal. The time required for the reaction is notcritical and may be varied between aboutfifte'en minutes and about eight hours, the length of time being dependent, of course, upon the solvent, the temperature, and the reducing agent.

' The mixtureis then hydrolyzed in conventional manner,

preferably the addition or an iceaud Water mixture pregnane-20-one-20-ketalelseparated from the reaction mixture by conventional procedure such as filtration or extraction; The solvent-used is one whichis-not reac tive under the reaction conditions, and' for'this gpurpose many are suitable, such as, for example, ether, benzene,

t'etrahydrofuran, dioxan, methanol, ethanol, isopropyl al:

In carryingout the hydrolysis process ofJthe prcsent invention, a novel 3,1 1fl-dihydi oxypregnane-ZQ ne-ZQ:

itetal obtained by the'above reduction process in'an organic solvent which is nonreactive under the conditions;

of reaction, such as, for example, methanol, ethanol, acetone, isopropyl alcohol, 'methyl ethyl 'ketone, dioxane, benzene, ether, and the like, or mixtures of these solvents, with benzeneethenor a benzene-ether-mixture be- -ing preferred, is admixed with an acid 'hydrolyzing agent i and water. The preferredacid hydrolyzing agents arethe mineral acids, such as, for example,*hydrochloric acid, sulfuric acid, phosphoric acid, and the like... iThe concentration of thehydrolyzing agent is not critical, and

solutions having a pH of about two up to solutions concentrated with respect tothe acid'are acceptable, the

range from 0.1 normal to two normal being preferred. 'The rate of reaction is greater when more concentrated acids are employed, although in such cases it'is advisable of addition of the reactants is not critical and any order dilute mineral acid, or the'like, and the 3,1113-dihydrdxy V drolysis of a 3,11B-dihydroxypregnane 20-one-20-ketal is i substantially quantitative, yields of above 97 percent being consistently obtained;

The following examples areillustrative of the process and compounds of the present invention but are not 'to be construed as limiting.

PREPARATION 1 3 a-HYDROXYPREGNANE l 1,20 D1oNE 20- ETHYLENBGLYCQL KETAL A mixture of 500 milligrams is inillirnoles) of 3 zfhy droxypregnane-l1,20-dione, one "milliliter [18,0 millimoles) of ethylene glycol, any milligrams of para-toluy enesulfonic'acid, andfifty milliliters of-benzene was refiuxed with agitation; for six hours: The Water which formed was r'emoyed jby co-distillationQwith benzene; The benzene solution was washed 'with water, drie'dand t concentrated. Recrystallization from a solvent mixture of ethyl acetate-hexane hydrocarbons (Skelly Solve: B) gave 310 milligrams (0.8 8 m illirnole) a percentyield,

of crude 3a-hydroXypregnane-11,20-dione-20;ethylene gly: col ketal, melting at 131 to 140 degrees 'centigrade, Upon further recrystallization, a purer producnmel'ting'at 142.5-144 degrees centigrade,.was obtained. 7 f In the same'rnanner as given inPreparation' 1, starting with a 3;; hydroxypregnane 11 ,20 -.dio ne and i the appro priate alkane diol, the following compounds are prepared;

7 3f? 7 hydroxypregnane 11,20 dione 20 'ethyle ne glycol .ketal, 3 t hydroxypr egnane l1,20 -jdione 20 -propanef diol k hydro yp a e .2 0: di ne 120- bu ne 2 -.di k al, y c yp gna e- 11, 0- dione -20 j pentane- -'1, 2 diol ketal, 3a ihydroxypreg' name 1 id p opa e 1,31f-.diul;k .ta

3a hydroxypregnane 11,20 dione -j20 {hepjtane -2,3-

diol ketal, 3a hydroxypregnane- 11,20 -1diorie 1 20 octane 1,2 diol ketal, and the like..

Example 1.' 3,11p dihydroxypregnizfie '20- one :20-

ethylene glycol ke'tal 7T0: a solution of 500 milligrams (thirteeninillimole's) of lithium 'aluminum'hydride in. fifty milliliters ofether was added'552'milligra ms (1.46 millimolesy of 351113 to employ a smaller amount of the acid used. The order of admixture of the starting ketaL'hydro'lyzing agent,'wa-

of thereaction mixture, temperatures of close to the boil- 7 In practice, the mixture of 3,11B-dihydroxypregnane ZO one-ZO-ketaI, solvent andhy drolyzing agent is usually heated to the boiling point and V subsequently permitted to stand at room temperature for several bouts. Altern atively, the reaction mixture may be warmed 'ata somewhat lower, temperature for a'longer In a general, the; reactionmixihydroxypregnaheiZOi-one :can' be sepaa rated: bylconventionalprocedure, E.

ii .gwhen the novel hydrolysis process preseriteim vention is carried out in'theabove-described rnanner,tlre

ne atin Xtoaypmgnane-ZQ-on. obtained byhy- V '1 lfi-hydroxy ketal is substantia'llyi c omple tegtheorganic solvent'is removed by con' venti o nal t, procedure, 1 preferably by evaporation under a a nitrogen or other inert atmosphere, toyield arsidue from V wh'i nthe'gtmtigrade.

, 1,2 {diol ketal instead of Sci droxypregnane 11,20 -;dion'e e20 ethylene-'glycolketal, prepared according tothe method of Preparation 11', in

fifteen milliliters of benzene, The reactionmixtureiwasi stirred for one hour at room, temperatureandihen re fluxedlfor'one hour. v Cautious addition; m me aijy,

hydrolyzed the reaction mixture. The precipitate; and

water were extracted with ether and thecomb ndfither solution was concentrated after washing and drying Bea; crystallizationfrom a mixed solvent of, ethyl acetate, hexane hydrocarbon (Skelly Solve B) gave a yield of i 30 I milligrams of 311,111; dihydroxypregnane qm jme"-"'20- ethylene glycol ketal, melting at 1525 154 degrees" .The infra-red dataco'nfirine'd thefpropose'd struc ture.

, Analysis-Percent calculated for c HggO 'q Example 2.1 40411 ti;-idiizydroxyprgrian 20 qua-+205 V propane ,2 diol ketal V In the mannerlo fiEx'anplejl :30 11 nane 20"- one .-'20'-' p'ropa'ne 1,2- diol ketalis prepared using 30: hydroxypregn'ane j- 11,20 -'dion'e ET- propanehexane-1,2 diol ketalI V "In the mannerof l ixample 1,311,113 Qd" oroxy p r ared 1,2 diol ketal instead of 3a -"hyd oxypregnane -11m); 1

dione I 20 ethylene glycol ketal;

V 7 ydrony pfegn'a'n e. 11,2,0- 'nione; 20-ethylerge-glycol ketal- Example 4.-3u,llfi dihydroxypregnane 20 one 20- propane 1,3 diol ketal In the same manner as given in Example 1,'3a,11[3- dihydroxypregnane 20 one 20 propane 1,3 diol ketal is prepared using 3a hydroxypregnane 11,20- dione 20 propane 1,3 diol ketal instead of 3afiydrloxypregnane 11,20 dione 20 ethylene glycol eta Example 5.3w11,8 dihyaroxypregnane 20 one 20- octane 1,2 diol ketal In the same manner as given in Example 1, 3a,11,8- dihydroxypregnane 20 one 20 octane 1,2 diol ketal is prepared using 3a hydroxypregnane 11,20- dione 20 octane 1,2 diol ketal instead of 3c: hydroxypregnane 11,20 dione 20 ethylene glycol ketal.

Example 6.3,B,11/3 dihydroxypregnane 20 one Z- ezhylene glycol ketal In the same manner as given in Example 1, 3,8,115- dihydroxypregnane one 20 ethylene glycol ketal is prepared from 3,8 hydroxypregnane 11,20 dione- 2O ethylene glycol ketal.

Example 7.-3a,]1,8 dihydroxypregnane 20 one 20- ethylene glycol ketal Example 8.-3a,11fl dz'hydroxypregnane Z0 one 20- ethylene glycol ketal In the same manner as given in Example 1, 301,115- dihydroxypregnane 20 one 20 ethylene glycol ketal is prepared from 3a hydroxypregnane 11,20 dione- 20 ethylene glycol ketal using lithium borohydride in an alcohol-water mixture instead of lithium aluminum hydride in an ether-benzene mixture. 7

In the manner of Examples 1 to 8, starting with the corresponding ketal, the following additional compounds are prepared: ,l 1B dihydroxypregnane 20 one 20- pentane 1,3 diol ketal, 3:1,116 dihydroxypregnane 20- one 20 butane 1,2 diol ketal, 3r1,11,6 dihydroxypregnane 20 one 20 heptane 1,2 diol ketal, 30,11B- dihydroxypregnane 20 one 3 methylpentane 1,2- diol ketal, 3u,11fl dihydroxypregnane 20 one 20- hexane 2,3 diol ketal, 305115 dihydroxypregnane 20- one 20 heptane 3,4 diol ketal, and the like.

xample 9.-3a,11;8 dihydroxypregnane 20 one A solution of 100 milligrams (0.25 millimole) of 311,115 dihydroxypregnane 20 one 20 ethylene glycol ketal from Example 1 was admixed with two drops of concentrated sulfuric acid (H two milliliters of water, and ten milliliters of methanol and the resulting mixture was warmed to the boiling point and then permitted to stand at room temperature for four hours. The methanol was evaporated under an atmosphere of nitrogen to give milligrams (a 99 percent yield) of 30,1lfl dihydroxypregnane 2O one, melting at 189-198 degrees centigrade. Recrystallization from methanol raised the melting point to 220-223 degrees centigrade. The infra-red analysis confirmed the proposed structure.

Example 10.30c,11;3 dihydroxypregnane 20 one A solution of 500 milligrams of 3a.,11 S dihydroxypregnane 20 one 20 ethylene glycol ketal, in a mixture of fifty milliliters of ether and fifteen milliliters of benzene, was stirred vigorously for sixteen hours at room temperature with 65 milliliters of dilute hydrochloric acid. At the end of this time the organic layer was separated, washed with water, dried and concentrated to give a percent yield of 3a,l1}3 dihydroxypregnane 20 one,

. 6 melting at 190-199 degrees centigrade. Recrystallization from methanol raised the melting point to 219-222 degrees centigrade.

Example 11.3u,11,8 dihya'roxypregnane 20 one To five-tenths (0.5) millimole of 3u,11,6 dihydroxypregnane 20 one 20 propane 1,2 diol ketal, prepared according to the procedure of Example 2, in ten milliliters of ethanol, was added eight drops of concentrated hydrochloric acid (HCl) and eight milliliters of water. The resulting admixture was heated to its boiling point and then permitted to stand for a period of eight hours at about thirty degrees centigrade. The solvent was evaporated under a nitrogen atmosphere to give 30;,11 3 dihydroxypregnane 20 one, melting at about 189-198 degrees centigrade, in 98 percent yield. Recrystallization from methanol raised the melting point to 220-223 degrees centigrade. The infra-red spectrum confirmed the theoretical structure.

Example 12.3a,11,B-dihydroxypregnane-ZO-one Following the procedure of Example 9, 3a,11p-dihydroxypregnane-ZO-one-ZO-propane-1,3-diol ketal, prepared according to the procedure of Example 4, is hydrolyzed to produce 3a,l1fi-dihydroxypregnane-ZO-one, having a melting point of 220-223 degrees Centigrade.

Example I 3.3 51,1 I,B-dihydroxypregnane-ZO-one In the same manner as given in Example 9, 3a,11fl-dihydroxypregnane20-one-20-butane-1,2,-diol ketal, prepared according to the procedure of Examples 1 to 8, is hydrolyzed to form 3a,1lB-dihydroxypregnane-ZO-one, having a melting point of 220-223 degrees centigrade.

Example 14.3p,1 1B-dihydroxypregnane-ZO-one Following the procedure outlined in Examples 9 through droxypregnane-ZO-one-ZO-ethylene glycol ketal, prepared according to the procedure of Example 6, is hydrolyzed to produce 35,11 S-dihydroxypregnane-ZO-one, having a melting point of 253-257 degrees Centigrade.

Following the procedure outlined in Examples 9 through 14, 3c,llfi-dihydroxypregnane-ZO-one is prepared from other 3a,11l8-dihydroxypregnane-20-one-20-ketals, such as, for example, 304,11fi-dihydroxypregnane-20-one-20-pentane-1,2-diol ketal, 3a,1lfi-dihydroxypregnane-ZO-one-ZO- hexane-1,2-diol ketal, 30,115-dihydroxypregnane-2O-one- 20-heptane-2,3-diol ketal, 3a,] lB-dihydroxypregnane-20- one-20-octane-1,2-diol ketal, and the like.

it is to be understood that the invention is not to be limited to the exact details of operation or exact compounds shown and described, as obvious modifications and equivalents will be apparent to those skilled in the art, and the invention is therefore to be limited only by the scope of the appended claims.

We claim:

1. A 3-hydroxypregnane-11,20-dione-20-keta1 having the following general formula:

CH3 O-(CHz).

wherein R is selected from the group consisting of hydrogen and lower-alkyl radicals containing from one to six carbon atoms, inclusive, R is selected from the group consisting of alpha and beta hydroxyl radicals, and n is an integer from one to two, inclusive.

2. 3fi-hydroxypregnane-11,20-dione-20-ethylene glycol ketal.

V a Ba-hydrOXypregnan'e-I1,2tl-dione-20-propane-1,3-diol ketal of the formula: 1 a

V to produce pregnane-llmi lfi diol 20-one-ethylene ketal;

" ketal group annin from. two; to eight, carbon atoms,

hydride, and lithium borohydride 'in a solvent at a tern peraturebelow"about lflodegrees centigrade, and isrflat- 7 ing a '3,l'lfi dihydroxypregnane%20 ne 20ketal"frorn the temperature'between'abontizero and about eighty degrees amount jtheoreticallylrequired,in an organic solvent at a temperaturebelow about 100 degreescentigrade, andiso- 1 V fthe feactionproducf."

t 2,824,871 V a Z r 3. Ba-hYdrQXypregnane-Il,20-dione-20;ethylene glycol ketalofi theiformula: pregnane-20 one-20 ethyleneglycol ketaleomprisingtreatcol ketal from the reaction product.

CH3 A; 1 ing 3b -hydroXypre g nane-11,20-dione-20-ethylene' glycol H: 0-01 1: 7: ketal'with lithium aluminum hydride in' exeess'et the 7 7 l a 5 amounttheoretically required, in an organic solvent at a V V r v 7 temperature below about 100 degrees centigrade,"and iso a i 'Q' lating 3a,'1 1fi-dihydroxypregnaneQO-bne-ZO-ethylene" gly- 10 pregnane-ZO-tgne-ZO-ketal comprisingtreating a 3-hydr0xy- ZO-ketal group contains from one to eight carbon atoms,

H A amount'the'oretically' required, in a'so'lvent at a tempera-' 4. B Q-hydrQXypregnane-I1;20-dione-2 0 propane-1,2-diol t'ure below about *100 degrees centigrade, and isolating a I i i" V 3,11,B-dihydrbxypregnane-ZO-ofie--ketal from-the reac ketal of the formula:

9 V 7 tion product. i V V a 1 933043131 12. .Aproc'ess for the preparation of 3,l1,8-dihydroxy V V pregnane-ZO-one-ZO-ketal comprising treating a 3-hydroxy- O;CH CHa pregnane-l1,20-dione-20-alkane diol ketal, wherein the 20-ketal group contains from two to eight carbon atoms, inclusive, with lithium borohydride in excess of the ture'below about degrees" centigrade, and isolating action product.

i ketal group containsjfrom two to eight carbon atornSQinelusive, with a reducing agent selected from the group consisting of lithium aluminum hydride, .sodiumboro- 6 A for the preparationzofpregnane}3:51ifi di 'ol-20-onecompr1smg treating ipregnane-3m-rol-l1,2(l-d1one a 3,11fl dihydroxypregnane 2() one 20 keta1 and with ethylene glycjol to prepare the correspondingzO-ethyifine i l" Se e ,redu'cing p a i acid hydrolyzing agent, in an aqueous organic solvent at dione-gtl-ethyleneketallwithinilithium aluminum hydride a 7. A iprocess for-the: preparation of 3,11fl-dihydro'x pregnaneQO-One ZO-Ketal comprising tre'at'ingfa S-hydroxypregnane-l1,20-dione-20-alkane diol-ketal, wherein the 20- dihydroxypregnaneQQ-one,

inc'lu'sive, ivithla reducing agent selected from the group consisting of lithium Valum'inum hydride, sodium bo'ro; V

lithium borohydride, in a solvent ata temperaturelbetween reaction product. 7, V a V V a e i J p 8. A process for theprepara'tion'of 3,11,3-dihydroxy pregnane-ZO-one-ZS-ethylene "glycol ketal, comprising V nane-ZO-one. f V V, tne group consisting of lithiurn'alurninum hydride, sodium V borohydride, and lithium' borohydride, in a solvent at a V sc m fllgififilc V V i V UNITED STATES PATENTS centigrade, and-isolating 3,11B-dihydroxypregnane-20-one-" 21288 4 i V t a r vSt'a've'ly VZO-ethylene glycol ketal from the reaction product. 7 a V V i a 9. A processfor the'preparatio n of 3,l'1,8-dihydroxy i gs ggg y f f i 2 pregnane-2ll onea20-ketal comprising trea'ting a 3-hydroxy- 1,8 Fmholz f 'j 19145 pregnane-l 1 ,2Q-dione-20-alkane diol ketal, wherein' the fi Miescher f r 7" b'? {952 V 20{k e t al; group contains from twof to eig ht carbon atoms, 75 2 Julian Afi 1 1 3 inclnsiye withilithium' aluminu'rn hydride in excess of the V i h g7 T e 2,648,663 i V a V OTHERZVREFERENCES, 1

lating" a' 13,1lfifdihydi oxypregnane-2Q-one-2Ol;etal from I 'Fieser et at; Natural Broduicts :10, A process for the preparation of -3a,1,1- dihydroxy- 11, A process for the preparation of 3,11B-dih'ydroxy 1 pregnane-lLZO-dioneQO-alkane diolketal, wherein the inclusive, with sodium borohyd'ride in excess ofthef or amount theoretically required, in a solvent at a tempera,

a 3,1 Ip-dihydroxypregnaneQO-on-ZO-ketal froin the re- 14. A processfor the preparation of;3,11;8-dihydroxy- 'pregnane-20-one :cornprising treating ;a 3-hydroxypregf nane-l-l,20-dione-20-alkane diol-ketal; wherein the 20- hydride, and lithium borohydride, in a solventata temperature below about'lOO'degrees centigrade to produce i 'drolyzing the thus-produced ZG-aIkane diol ketal with, an:

a temperatureb'etween about izero degrees centigrade and theb-oilingpoint of thereaction mixture, to obtain 3,116 7 Pregnane-Z O-Qrie comprising treating 3-hydroxypregna'rie V 111,20 dione-20-ethylene glycol ketal with an excess of a reducing agent selected 'from the "group c'onsis'ting of V lithiuma'luminum hydride, sodium borohydride {and about zero and about eighty degrees centigrade, .toproduce f 3,11B-dihydroxypregnane-ZO-one-ZO-ethylene glycol'lcetaLf: and hydrolyzing thethus-produced 2 O- ethy lene glycol p ketal withja mineral acid,-'in an aqueous organigsolvent1 '7 7 at a temperature between about zero and theboilingpoin tz" 1 wtreatmg y yP e a -e y u g s .of thereactionmixture, to obtain;3,l,l 9-dihydroxypreg-' 1 'col ketalwith an excess of'a r'educing'agent selected from Y ,1 I i Mia-a a ;13. A process for the preparation .of'3,11B- dihydroxyf pregnane-20 one comprising treating a' 3-hydroxy'p're'gmane-11,2O-dione-ZO-alkane :diol ketal 'with fa reducin'g i'; j agent selected from the group consisting of lithium alumi H i i f nurn;hydride,- sodium 'borohydride andilithium borohyi" V E 7, V dride topro duce a 3,1I B-dihydrOXypregnane-Z0-one 2O1 C i alkane diol ketal, and hydroly ing' the thus -produced 20 alkanediol ketal with an acid hydrolyzing agent reproduce UNITED STATES PATENT OFFICE Certificate of Correction Patent No. 2,824,871 February 25, 1958 Robert H. Levin et a1.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 6, lines 35 and 36, for procedure outlined in Examples 9 through droxypregnaneread procedure of Example 9, 3B,11,8-d1hydroxypregnane- Signed and sealed this 11th day of November 1958.

Attest= KARL H. AXLINE,v ROBERT C. WATSON,

Attesting Ofioer. C'ommz'ssz'oner of Patents. 

6. A PROCESS FOR THE PREPARATION OF PREGNANE-3A,11B-DIOL-20-ONE COMPRISING TREATING PREGNANE-3A-OL-11,20-DIONE WITH ETHYLENE GLYCOL TO PREPARE THE CORRESPONDING 20-ETHYLENE KETAL, SELECTIVELY REDUCING THE PREGNANE-3A-OL-11,20DIONE-20-ETHYLENE KETAL WITHIN LITHIUM ALUMINUM HYDRIDE TO PRODUCE PREGNANE-3A,11B-DIOL-20-ONE-ETHYLENE KETAL. 